Membrane glycoproteins seem to play a major role in the mediation of interactions, such as contact inhibition, between cells. One hallmark of cancer cells is a loss of contract inhibition. Interaction with the external carbohydrate moieties of cell surface glycoproteins, such as by plant lectins, leads to alteration in internal physiological state, e.g. to transformation of lymphocytes. Previous work by the PI was instrumental in demonstrating that the MN-glycoprotein (glycophorin) of the human red cell membrane is vectorially oriented in a trasmembrane fashion with its carbohydrate-rich NH2-terminus outside and its COOH-terminus exposed to the cytoplasm. The basic orientation of MN-glycoprotein is therefore suitable for influencing intracellular events from outside the cell. The PI has further shown that association of the membrane-spanning hydrophobic segment of MN-glycoprotein with bilayer membranes results in the production of torus-shaped intramembranous structures with central cavities (visualized by freeze-fracture electron microscopy). These structures are similar to the so-called intramembranous particles present in most mammalian membranes. The intrabilayer torus particles derived from MN-glycoprotein have been shown by the PI to be multimeric polypeptide structures which, on the basis of preliminary evidence, seem to form aqueous transmembrane pores. The purpose of the present proposal is to continue work currently under way in the PI's laboratory to test the multimeric pore model for the hydrophobic domain of MN-glycoprotein. In addition support is sought for associated studies underway to examine the physical chemical properties of the interaction of intact MN-glycoprotein with membrane bilayers. In addition to providing a specific testable model for mediation of transmembrane events, the proposed studies will be highly relevant to an understanding of the basic principles underlying protein-lipid interactions in membranes. Techniques to be used in the proposed investigations incude bilayer lipid membrane studies, NMR, fluorescence and ESR probe and chemical cross-linking experiments and low angle X-ray studies.